Post-Graduate Training
Internship, Medicine, Hospital of the University of Pennsylvania, 1994-1995.
Resident, Medicine, Hospital of the University of Pennsylvania, 1995-1996.
Fellow, Gastroenterology, Hospital of the University of Pennsylvania, 1996-2000.

Description of Research Expertise

Research Interests

1. Mechanisms of intestinal metaplasia of the esophagus (Barrett’s esophagus) and stomach, with a focus on developing novel cell culture and animal models for this disorder.
2. Role of myeloid derived suppressor cells in the pathogenesis of barrett’s esophagus and esophageal adenocarcinoma.
3. autophagy in the pathogenesis of Barrett’s esophagus, progression to neoplasia, and resistance to therapies.
4. Modeling the effects of Cox-2 activity on oxidative stress and DNA damage in the esophagus.
5. Identification of cells and factors contributing to the intestinal stem cell niche, and their response to injury and disease conditions.
6. Live-cell imaging studies of intestinal stem cell and crypt niche cell interactions, crypt fissioning, mitosis, and early events in neoplastic transformation by confocal microscopy.

Description of Research

Barrett’s Esophagus Focus:
Esophageal adenocarcinoma (EAC) has been the fastest rising malignancy in the U.S.. Several conditions increase the risk for the development of EAC, including obesity, smoking, diet, acid reflux, and, most significantly, Barrett's esophagus (BE). BE occurs at the gastroesophageal (GE) junction and is the replacement of normal squamous esophageal mucosa with an intestinalized columnar epithelium. It typically arises in response to chronic acid exposure and is associated with acid reflux. Importantly, the histologic precursor lesions and molecular mechanisms underpinning BE pathogenesis remain poorly understood. One reason is the paucity of experimental models for BE. Our research has focused on this problem, and the development of innovative, genetically based and physiologically relevant human cell based 3D organotypic cultures and transgenic mouse models for BE is an important objective of my lab. We are broadly pursuing several strategies including exploring the role proinflammatory cytokines (IL-1beta), eicosanoids (Cox-2), myeloid derived suppressor cells, and autophagy in BE pathogenesis and progression to neoplasia.

Intestinal Stem Cell Focus:
Stem cells are defined by the capacity for long-term self-renewal and multilineage differentiation. Until relatively recently, our understanding of stem cell biology, as well as their role in many human disease processes from aging to cancer, has been rather limited. Moreover, interest in harnessing the stem cell’s capacity for self-renewal to promote organ and tissue regeneration cuts across many medical disciplines. Genetic studies have identified several robust markers for stem cell populations in the intestine. These advances now make it possible to isolate stem cell populations for more advanced molecular investigations and ex vivo culture. We are presently developing human multi-cell based 3D culture systems in which we can model inflammatory conditions of the gut as a method of studying physiologically the effects of immune cells, inflammatory microenvironment, oxidative stress and mitochondrial dysfunction on stem cell biology and stem cell DNA damage. Recently we have also begin using live cell confocal microscopy to investigate how the intestinal stem cell niche is established, the relationship between niche and stem cells, how intestinal crypts fission, how stem cells undergo mitosis, and early events in neoplastic transformation.